Savella Approved for Fibromyalgia in 2009

The drug is an alternative when other drugs don't work.

By Mary Anne Dunkin

People with fibromyalgia whose symptoms don’t respond well to other therapies have had another option since January 2009 when the Food and Drug Administration (FDA) approved milnacipran HCl (Savella) to help manage the pain and fatigue associated with this disorder.

Milnacipran became the third drug to be approved by the FDA for fibromyalgia. It was the first drug to be newly introduced into the United States specifically for use in fibromyalgia, says Daniel Clauw, MD, professor of medicine in the division of rheumatology at the University of Michigan in Ann Arbor.

In the studies that led to its approval, milnacipran was shown to be safe and effective in two phase-3 studies involving more than 2,000 people living with fibromyalgia. In the studies, dosages of 100 milligrams (mg) per day and 200 mg per day demonstrated significant improvements in pain, patient global assessment and physical function. The most common adverse reaction to the drug was nausea. Other common side effects were constipation, dry mouth, excessive sweating, hot flushes, hypertension, increased heart rate and palpitations, and vomiting.

Milnacipran belongs to a class of drugs called selective serotonin and norepinephrine reuptake inhibitors. Although it’s still not clear exactly how these drugs work, some researchers believe they may help to correct abnormalities in certain brain neurotransmitters may be central to this pain disorder.

“Savella has been approved as an antidepressant for some time in many countries, but not in the United States,” says Dr. Clauw who was hired by Cypress Biosciences (now the U.S. licensor of milnacipran) to identify a safe, existing drug that had a profile that should make it effective in fibromyalgia. Dr. Clauw is also a member of Arthritis Today’s medical advisory board.

While milnacipran has not been tested head to head with other antidepressants, Dr. Clauw says there is evidence to suggest it may be more effective against the symptoms associated with fibromyalgia than other antidepressants, including other selective serotonin and norepinephrine reuptake inhibitors.

“Many animal and other studies suggest this drug may have – relative to serotonin – more norepinephrine reuptake properties,” says Dr. Clauw. “Many scientists feel that norepinephrine may be a more important neurotransmitter to modulate in chronic pain states than serotonin.”

“Norepinephrine activity may also better able to relieve symptoms such as fatigue and memory difficulties,” he says. “We won't really know if these effects seen in animal studies really translate into better improvement in these symptoms until further testing is performed.”

But other experts believe caution is warranted for this and other fibromyalgia drugs.

“The problem with most treatments for fibromyalgia is that they tend to work well in the short term,” says Frederick Wolfe, MD, Director of the National Data Bank for Rheumatic Diseases in Wichita, Kan. “These drugs have not been shown to be effective in the long run.”

People with fibromyalgia whose symptoms don’t respond well to other therapies have had another option since January 2009 when the Food and Drug Administration (FDA) approved milnacipran HCl (Savella) to help manage the pain and fatigue associated with this disorder.

Milnacipran became the third drug to be approved by the FDA for fibromyalgia. It was the first drug to be newly introduced into the United States specifically for use in fibromyalgia, says Daniel Clauw, MD, professor of medicine in the division of rheumatology at the University of Michigan in Ann Arbor.

In the studies that led to its approval, milnacipran was shown to be safe and effective in two phase-3 studies involving more than 2,000 people living with fibromyalgia. In the studies, dosages of 100 milligrams (mg) per day and 200 mg per day demonstrated significant improvements in pain, patient global assessment and physical function. The most common adverse reaction to the drug was nausea. Other common side effects were constipation, dry mouth, excessive sweating, hot flushes, hypertension, increased heart rate and palpitations, and vomiting.

Milnacipran belongs to a class of drugs called selective serotonin and norepinephrine reuptake inhibitors. Although it’s still not clear exactly how these drugs work, some researchers believe they may help to correct abnormalities in certain brain neurotransmitters may be central to this pain disorder.

“Savella has been approved as an antidepressant for some time in many countries, but not in the United States,” says Dr. Clauw who was hired by Cypress Biosciences (now the U.S. licensor of milnacipran) to identify a safe, existing drug that had a profile that should make it effective in fibromyalgia. Dr. Clauw is also a member of Arthritis Today’s medical advisory board.

While milnacipran has not been tested head to head with other antidepressants, Dr. Clauw says there is evidence to suggest it may be more effective against the symptoms associated with fibromyalgia than other antidepressants, including other selective serotonin and norepinephrine reuptake inhibitors.

“Many animal and other studies suggest this drug may have – relative to serotonin – more norepinephrine reuptake properties,” says Dr. Clauw. “Many scientists feel that norepinephrine may be a more important neurotransmitter to modulate in chronic pain states than serotonin.”

“Norepinephrine activity may also better able to relieve symptoms such as fatigue and memory difficulties,” he says. “We won't really know if these effects seen in animal studies really translate into better improvement in these symptoms until further testing is performed.”

But other experts believe caution is warranted for this and other fibromyalgia drugs.

“The problem with most treatments for fibromyalgia is that they tend to work well in the short term,” says Frederick Wolfe, MD, Director of the National Data Bank for Rheumatic Diseases in Wichita, Kan. “These drugs have not been shown to be effective in the long run.”